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Comparative DNA sequence analysis of mouse and human protocadherin gene clusters
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Genome Research
|March 7, 2001
Summary
Comparative genomic analysis reveals conserved regulatory elements in human and mouse protocadherin gene clusters, suggesting shared mechanisms for gene expression control.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Protocadherin (Pcdh) gene clusters share structural similarities with immunoglobulin and T-cell receptor genes.
- Pcdh proteins have distinct extracellular/transmembrane domains encoded by large variable exons and intracellular domains by smaller constant exons.
Purpose of the Study:
- To compare the genomic organization of human and mouse protocadherin alpha, beta, and gamma gene clusters.
- To identify conserved DNA sequences and regulatory motifs within these gene clusters.
Main Methods:
- Comparative DNA sequence analysis of human (750 kb) and mouse (900 kb) Pcdh gene clusters.
- Identification and localization of conserved sequences, DNA sequence motifs, and CpG islands.
Main Results:
- Human and mouse Pcdh alpha and gamma clusters are nearly identical; the mouse Pcdh beta cluster is larger and contains more genes.
- Conserved DNA sequences upstream of variable region exons are more conserved between orthologs than paralogs.
- A highly conserved DNA sequence motif exists upstream of each variable region exon's translation start site.
- CpG islands are abundant in variable regions, correlating with exon positions.
Conclusions:
- The conserved upstream motifs and CpG islands suggest distinct, conserved promoters regulate each variable region exon.
- These findings support conserved mechanisms for protocadherin gene expression regulation between human and mouse.
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